Neurological disorders in humans are often difficult to study in human brains. As a result, animal models need to be used to simulate the workings of the human nervous system. Usually, scientists will rely on mice, but recently, the use of zebrafish has become popular due to the animal's utility.

Charcot—Marie—Tooth disease (CMT) is causes by a hereditary genetic disorder that affects the nerves that branch throughout the body in young adults. The disease leads to nerve damage and causes a weakness of muscles, foot and hand deformity, loss of muscle mass, and numbness in the lower body. CMT eventually leads to disability and a loss in sensation in the places most affected.

A new study using zebrafish, done by Andrew Grierson, Ph.D., of University of Sheffield, has revealed a great deal about CMT and potential therapies. Humans and zebrafish have proteins that are 82 percent alike — this is important because it indicates that zebrafish are suitable in studies that compare results to potential treatments for diseases in humans. When researchers altered the genes of zebrafish to be the same as patients of CMT, similar symptoms were seen as the fish aged. Once they matured into adulthood, the fish lost the ability to swim properly. The scientists feel that the difficulties in swimming can be paralleled to the difficulties humans face in walking after CMT has fully developed.

Using the zebrafish, researchers were able to identify what goes wrong in neurons as a result of CMT for the first time. They saw that the myelin sheaths around neurons began to degrade. Similarly, the far branches of nerve cells also started to degrade, leading to the sensations of pain, as messages like sensation could not travel up and down this part of the neuron anymore. Both of these issues led to the pain and neurodegeneration suffered by CMT patients.

The researchers have said that all of this would not have been clear in any other animal. In other animals, the disease starts its effects very early in development, but in humans, disease onset is usually in adolescence. This difference in other animals skews results and makes findings inconsistent with the disease's effects in humans. Grierson said, "Using zebrafish we were able to develop a model with an adult onset, progressive phenotype with predominant symptoms of motor dysfunction similar to [what happens in humans]."

He added that while we know much about other neurodegenerative diseases, others seem to escape our grasp. "Motor neurons are the largest cells in our bodies, and as such they are highly dependent on a cellular transport system to deliver molecules through the long nerve cell processes which connect the spinal cord to our muscles," he continued. "We already know that defects in the cellular transport system occur early in the development of diseases such as Alzheimer's disease, Motor Neuron Disease and spastic paraplegia. Using our zebrafish model we have found that similar defects in transport are also a key part of the disease process in CMT

Now that so much has been found out about the way CMT changes neurons for the worst, researchers can start to develop targeted therapies and treatments for the disease. There is currently no cure for CMT, nor are there any drugs that can help manage its symptoms. Patients often depend on physical or occupational therapies or surgeries for relief from symptoms.

While a cure may not be made tomorrow, the prospect of it and improved disease management therapies now exist.

Source: Chapman AL, Bennett EJ, Ramesh T, De Vos KJ, Grierson AJ. Axonal Transport Defects in a Mitofusin 2 Loss of Function Model of Charcot-Marie-Tooth Disease in Zebrafish. PLOS ONE. 2013.